A peptide fragment of human prion protein, HuPrP(106-126), has been reported to mimic the pathological features underlying prion diseases. Although the actual neurotoxic mechanism of HuPrP(106-126) has not been elucidated, several hypotheses has been proposed based on the role for copper. In this study, to understand the toxic function of HuPrP(106-126) from a viewpoint of electrochemical competence, we investigated redox properties of copper ion complexes with four different binding motifs of a model of HuPrP(106-126) based on density functional theory calculations. We found that the HuPrP(106-126)derived models exhibited diverse redox activities that depended on copper-binding conformations. (C) 2010 Elsevier B. V. All rights reserved.